The area of inorganic pharmaceuticals is in its infancy. The most common and well studied inorganic pharmaceutical is cis-platinum, an anticancer drug (Lippard, Science 218:1075-1082 (1982); Rosenberg, Nature 222:385 (1969); Cleare et al., Bioinorg. Chem. 2:187 (1973)). This inorganic pharmaceutical is clinically used to treat a variety of cancers. The mode of action of cis-platinum is believed to be by interacting with DNA to prevent the cell from proliferating.
Three gold compounds have also been investigated and clinically used to treat arthritis (Dash Metal Ions Biol. Systm. 14:179 (1982); Elder et al., Chem. Rev. 87:1027 (1987)). These include Auranofin, a gold sodium thiomalate and a gold thioglucose compound, depicted below: ##STR1##
The current understanding on the therapeutic action of gold compounds to treat arthritis is limited. The mode of action of anti-arthritic gold drugs is largely unknown, but it may involve binding of Au(I) to protein thiol groups, thus inhibiting the formation of disulfide bonds, and could lead to denaturation and subsequent formation of macroglobulins. See Bioinorganic Chemistry (Eds Bertini, Gray, Lippard, and Valentine, pg 519, 1994).
A class of cobalt (III) schiff-base compounds have been reported to have antivirial, antitumor, and antimicrobial activities, as well as antiinflammatory properties (see U.S. Pat. Nos. 4,866,054; 4,866,053; 5,049,577; 5,106,841; 5,142,076; and 5,210,096).